The evolution of two Trypanosoma cruzi subgroups inferred from rRNA genes can be correlated with the interchange of American mammalian faunas in the Cenozoic and has implications to pathogenicity and host specificity.

The agent of Chagas disease, Trypanosoma cruzi, is divided into two highly divergent genetic subgroups, lineages 1 and 2, which include all typed strains isolated from humans, insect vectors, and sylvatic mammals. The evolutionary origin of these two T. cruzi lineages and the clinical importance of their identification, have been the subject of intense debate. Here, using molecular phylogenetic analysis, we found that the distance between the two T. cruzi lineages is equivalent to the distance between genera Leishmania and Endotrypanum. Also, we confirmed that T. rangeli is more closely related to T. cruzi than to T. brucei using the rDNA sequence from a human strain of T. rangeli. Phylogenetic trees based on small subunit rDNA sequences further suggest that the two T. cruzi lineages diverged between 88 and 37 million years (Myr) ago. We hypothesize that lineage 2 is indigenous to South America while lineage 1 has been introduced to South America recently, along with North American placental mammals, after the connection of the Americas in the Pliocene (5 Myr ago) or with caviomorph rodents and primates in the Oligocene (38 Myr ago). This would explain the preferential association of T. cruzi lineage 2 with marsupials and of lineage 1 with human disease. These two T. cruzi lineages are likely to be distinct species, or at least subspecies, because of their different ecological and epidemiological traits and estimated long period of independent evolution.